This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adenocarcinomas of the esophagus and adenocarcinomas of the gastroesophageal junction are postulated to be complex genetic diseases. Combined influences of environmental factors and genetic susceptibility likely influence the age at which these cancers develop. Initially we determined whether familiality and other recognized risk factors are associated with the development of these cancers at an earlier age. A structured validated questionnaire was utilized to collect self reported data on gastroesophageal reflux symptoms, risk factors for Barrett's esophagus (BE) and family history, including age of cancer diagnosis in affected relatives from probands with BE, adenocarcinoma of the esophagus, or adenocarcinoma of the gastro-esophageal junction, at five tertiary care academic hospitals. Medical records of all relatives reported to be affected were requested from hospitals providing this cancer care to confirm family histories. Familiality of BE/cancer, obesity (defined as body mass index >30), gastro-esophageal reflux symptoms, and other risk factors were assessed for association with a young age of cancer diagnosis. There were no significant differences in symptoms of gastroesophageal reflux, body mass index, race, gender, and smoking history between familial and non-familial cancers. However, mean age of cancer diagnosis was significantly younger comparing those who were obese one year prior to diagnosis with those who were non-obese, mean age 58.99 yrs vs. 63.6 yrs, p = 0.008. Multivariable modeling of age at cancer diagnosis showed that obesity 1 year before diagnosis was associated with a younger age of cancer diagnosis (p=0.005) after adjustment for heartburn and regurgitation duration.